The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction
Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of its expression appear to correlate with disease progression and metastasis. However, the role of SHH in bone destruction associated with oral squamous cell carcinomas is still unclear. In th...
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| creator | Shimo, Tsuyoshi Matsumoto, Kenichi Takabatake, Kiyofumi Aoyama, Eriko Takebe, Yuichiro Ibaragi, Soichiro Okui, Tatsuo Kurio, Naito Takada, Hiroyuki Obata, Kyoichi Pang, Pai Iwamoto, Masahiro Nagatsuka, Hitoshi Sasaki, Akira |
| description | Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of its expression appear to correlate with disease progression and metastasis. However, the role of SHH in bone destruction associated with oral squamous cell carcinomas is still unclear. In this study we analyzed SHH expression and the role played by SHH signaling in gingival carcinoma-induced jawbone destruction. From an analysis of surgically resected lower gingival squamous cell carcinoma mandible samples, we found that SHH was highly expressed in tumor cells that had invaded the bone matrix. On the other hand, the hedgehog receptor Patched and the signaling molecule Gli-2 were highly expressed in the osteoclasts and the progenitor cells. SHH stimulated osteoclast formation and pit formation in the presence of the receptor activator for nuclear factor-κB ligand (RANKL) in CD11b+ mouse bone marrow cells. SHH upregulated phosphorylation of ERK1/2 and p38 MAPK, NFATc1, tartrate-resistant acid phosphatase (TRAP), and Cathepsin K expression in RAW264.7 cells. Our results suggest that tumor-derived SHH stimulated the osteoclast formation and bone resorption in the tumor jawbone microenvironment. |
| doi_str_mv | 10.1371/journal.pone.0151731 |
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However, the role of SHH in bone destruction associated with oral squamous cell carcinomas is still unclear. In this study we analyzed SHH expression and the role played by SHH signaling in gingival carcinoma-induced jawbone destruction. From an analysis of surgically resected lower gingival squamous cell carcinoma mandible samples, we found that SHH was highly expressed in tumor cells that had invaded the bone matrix. On the other hand, the hedgehog receptor Patched and the signaling molecule Gli-2 were highly expressed in the osteoclasts and the progenitor cells. SHH stimulated osteoclast formation and pit formation in the presence of the receptor activator for nuclear factor-κB ligand (RANKL) in CD11b+ mouse bone marrow cells. SHH upregulated phosphorylation of ERK1/2 and p38 MAPK, NFATc1, tartrate-resistant acid phosphatase (TRAP), and Cathepsin K expression in RAW264.7 cells. Our results suggest that tumor-derived SHH stimulated the osteoclast formation and bone resorption in the tumor jawbone microenvironment.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0151731</identifier><identifier>PMID: 27007126</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acid phosphatase ; Acid phosphatase (tartrate-resistant) ; Acid resistance ; Animals ; Biocompatibility ; Biology and Life Sciences ; Bone growth ; Bone marrow ; Bone matrix ; Bone resorption ; Bone surgery ; Cancer therapies ; Carcinoma, Squamous Cell - pathology ; Carcinoma, Squamous Cell - physiopathology ; Cathepsin K ; CD11b antigen ; Cell Differentiation - physiology ; Cell Line ; Cell Proliferation ; Cells (biology) ; Cellular signal transduction ; Dentistry ; Destruction ; Growth factors ; Hedgehog protein ; Hedgehog Proteins - physiology ; Humans ; Jaw ; Jawbone ; Kinases ; Mandible ; Mandibular Neoplasms - pathology ; Mandibular Neoplasms - physiopathology ; MAP kinase ; Maxillofacial surgery ; Medical prognosis ; Medicine ; Medicine and Health Sciences ; Metastases ; Metastasis ; Mice ; Oral carcinoma ; Oral squamous cell carcinoma ; Osteoclastogenesis ; Osteoclasts ; Osteoclasts (Biology) ; Osteoclasts - cytology ; Osteogenesis ; Osteoprogenitor cells ; Pathology ; Patients ; Pharmaceutical sciences ; Phosphorylation ; Proteins ; Signal Transduction - physiology ; Signaling ; Sonic hedgehog ; Squamous cell carcinoma ; TRANCE protein ; Tumor cells ; Tumors ; University graduates</subject><ispartof>PloS one, 2016-03, Vol.11 (3), p.e0151731-e0151731</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Shimo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Shimo et al 2016 Shimo et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-15d2af1b346b47a70747a3d11394d27054c3d507ada7655552ce28d8e0d31d53</citedby><cites>FETCH-LOGICAL-c692t-15d2af1b346b47a70747a3d11394d27054c3d507ada7655552ce28d8e0d31d53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805186/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805186/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27007126$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tuukkanen, Juha</contributor><creatorcontrib>Shimo, Tsuyoshi</creatorcontrib><creatorcontrib>Matsumoto, Kenichi</creatorcontrib><creatorcontrib>Takabatake, Kiyofumi</creatorcontrib><creatorcontrib>Aoyama, Eriko</creatorcontrib><creatorcontrib>Takebe, Yuichiro</creatorcontrib><creatorcontrib>Ibaragi, Soichiro</creatorcontrib><creatorcontrib>Okui, Tatsuo</creatorcontrib><creatorcontrib>Kurio, Naito</creatorcontrib><creatorcontrib>Takada, Hiroyuki</creatorcontrib><creatorcontrib>Obata, Kyoichi</creatorcontrib><creatorcontrib>Pang, Pai</creatorcontrib><creatorcontrib>Iwamoto, Masahiro</creatorcontrib><creatorcontrib>Nagatsuka, Hitoshi</creatorcontrib><creatorcontrib>Sasaki, Akira</creatorcontrib><title>The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of its expression appear to correlate with disease progression and metastasis. However, the role of SHH in bone destruction associated with oral squamous cell carcinomas is still unclear. In this study we analyzed SHH expression and the role played by SHH signaling in gingival carcinoma-induced jawbone destruction. From an analysis of surgically resected lower gingival squamous cell carcinoma mandible samples, we found that SHH was highly expressed in tumor cells that had invaded the bone matrix. On the other hand, the hedgehog receptor Patched and the signaling molecule Gli-2 were highly expressed in the osteoclasts and the progenitor cells. SHH stimulated osteoclast formation and pit formation in the presence of the receptor activator for nuclear factor-κB ligand (RANKL) in CD11b+ mouse bone marrow cells. SHH upregulated phosphorylation of ERK1/2 and p38 MAPK, NFATc1, tartrate-resistant acid phosphatase (TRAP), and Cathepsin K expression in RAW264.7 cells. 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However, the role of SHH in bone destruction associated with oral squamous cell carcinomas is still unclear. In this study we analyzed SHH expression and the role played by SHH signaling in gingival carcinoma-induced jawbone destruction. From an analysis of surgically resected lower gingival squamous cell carcinoma mandible samples, we found that SHH was highly expressed in tumor cells that had invaded the bone matrix. On the other hand, the hedgehog receptor Patched and the signaling molecule Gli-2 were highly expressed in the osteoclasts and the progenitor cells. SHH stimulated osteoclast formation and pit formation in the presence of the receptor activator for nuclear factor-κB ligand (RANKL) in CD11b+ mouse bone marrow cells. SHH upregulated phosphorylation of ERK1/2 and p38 MAPK, NFATc1, tartrate-resistant acid phosphatase (TRAP), and Cathepsin K expression in RAW264.7 cells. Our results suggest that tumor-derived SHH stimulated the osteoclast formation and bone resorption in the tumor jawbone microenvironment.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27007126</pmid><doi>10.1371/journal.pone.0151731</doi><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_plos_journals_1775365408 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acid phosphatase Acid phosphatase (tartrate-resistant) Acid resistance Animals Biocompatibility Biology and Life Sciences Bone growth Bone marrow Bone matrix Bone resorption Bone surgery Cancer therapies Carcinoma, Squamous Cell - pathology Carcinoma, Squamous Cell - physiopathology Cathepsin K CD11b antigen Cell Differentiation - physiology Cell Line Cell Proliferation Cells (biology) Cellular signal transduction Dentistry Destruction Growth factors Hedgehog protein Hedgehog Proteins - physiology Humans Jaw Jawbone Kinases Mandible Mandibular Neoplasms - pathology Mandibular Neoplasms - physiopathology MAP kinase Maxillofacial surgery Medical prognosis Medicine Medicine and Health Sciences Metastases Metastasis Mice Oral carcinoma Oral squamous cell carcinoma Osteoclastogenesis Osteoclasts Osteoclasts (Biology) Osteoclasts - cytology Osteogenesis Osteoprogenitor cells Pathology Patients Pharmaceutical sciences Phosphorylation Proteins Signal Transduction - physiology Signaling Sonic hedgehog Squamous cell carcinoma TRANCE protein Tumor cells Tumors University graduates |
| title | The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T22%3A06%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Role%20of%20Sonic%20Hedgehog%20Signaling%20in%20Osteoclastogenesis%20and%20Jaw%20Bone%20Destruction&rft.jtitle=PloS%20one&rft.au=Shimo,%20Tsuyoshi&rft.date=2016-03-23&rft.volume=11&rft.issue=3&rft.spage=e0151731&rft.epage=e0151731&rft.pages=e0151731-e0151731&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0151731&rft_dat=%3Cgale_plos_%3EA453470555%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1775365408&rft_id=info:pmid/27007126&rft_galeid=A453470555&rft_doaj_id=oai_doaj_org_article_f17bdda213e94270ab49870a003f059c&rfr_iscdi=true |